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Liver Kinetics of Glucose Analogs Measured in Pigs by PET: Importance of Dual-Input Blood Sampling

PET-Center and Department of Medicine V, Aarhus University Hospital, and Institute for Experimental Clinical Research, Aarhus University, Aarhus, Denmark; and Department of Mathematics, University of Queensland, Brisbane, Australia

Metabolic processes studied by PET are quantified traditionally using compartmental models, which relate the time course of the tracer concentration in tissue to that in arterial blood. For liver studies, the use of arterial input may, however, cause systematic errors to the estimated kinetic parameters, because of ignorance of the dual blood supply from the hepatic artery and the portal vein to the liver. Methods: Six pigs underwent PET after [¹⁵O]carbon monoxide inhalation, 3-O-[¹¹C]methylglucose (MG) injection, and [¹⁸F]FDG injection. For the glucose scans, PET data were acquired for 90 min. Hepatic arterial and portal venous blood samples and flows were measured during the scan. The dual-input function was calculated as the flow-weighted input. Results: For both MG and FDG, the compartmental analysis using arterial input led to systematic underestimation of the rate constants for rapid blood–tissue exchange. Furthermore, the arterial input led to absurdly low estimates for the extracellular volume compared with the independently measured hepatic blood volume of 0.25 ± 0.01 mL/mL (milliliter blood per milliliter liver tissue). In contrast, the use of a dual-input function provided parameter estimates that were in agreement with liver physiology. Using the dual-input function, the clearances into the liver cells (K₁ = 1.11 ± 0.11 mL/min/mL for MG; K₁ = 1.07 ± 0.19 mL/min/mL for FDG) were comparable with the liver blood flow (F = 1.02 ± 0.05 mL/min/mL). As required physiologically, the extracellular volumes estimated using the dual-input function were larger than the hepatic blood volume. The linear Gjedde–Patlak analysis produced parameter estimates that were unaffected by the choice of input function, because this analysis was confined to time scales for which the arterial-input and dual-input functions were very similar. Conclusion: Compartmental analysis of MG and FDG kinetics using dynamic PET data requires measurements of dual-input activity concentrations. Using the dual-input function, physiologically reasonable parameter estimates of K₁, k₂, and V_p were obtained, whereas the use of conventional arterial sampling underestimated these parameters compared with independent measurements of hepatic flow and hepatic blood volume. In contrast, the linear Gjedde–Patlak analysis, being less informative but more robust, gave similar parameter estimates (K, V) with both input functions.

Key Words: liver glucose metabolism • FDG kinetics • compartment model • PET • liver blood flow

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